A large number of biologically active classes of natural products, among which are the harmila alkaloids, the ergolines, the mitomicins and many others derive biologically from the amino acid, tryptophan. The essential parent heterocyclic skeleton of all of these compounds is indole, a simple heteroaromatic compound isolated originally from coal tar. Indole derivatives of neurological significance include serotonin, lysergic acid and its derivatives, dimethyltryptamine, and reserpine. This study concentrates on syntheses of potentially active reagents related to indole but containing a sulfur atom. In Part I of the proposal, syntheses and testing of indole - cyclobutenes related, by a simple cyclobutene - butadiene ring opening to the benzodiazepines are proposed. Lipid solubility in these compounds can be controlled by structural modification in a rather general photochemical synthesis, thus the effect of polarity and stereochemistry on the activity of benzodiazepine precursors can be systematically studied. The compounds will be tested or pharmacological activity similar to that possessed by diazepam. A variety of animal test systems will be employed including behavior and motor performance in cats, dose response and lethality in mice, anticonvulsant activity and spinal reflux measurements. Systematic synthesis and testing of novel benzodiazepine precursors may provide new compounds with some degree of specificity for one of the clinically useful actions of these drugs. Benzodiazepines are useful because of their antianxiety, anticonvulsant, muscle relaxant, sedative and hypontic properties. A compound's usefulness is maximized if it can be made highly selective. For example, and anticonvulsant with no other benzodiazepine actions would be extremely desirable. Likewise, a centrally acting muscle relaxant devoid of sedative properties would be a major advance in treating a wide variety of medical and surgical patients. Despite the different suggested uses for the various benzodiazepines (diazepam for anxiety, muscle spasm and ethanol withdrawal, clonazepam for certain types of seizure disorders, flurazepam for sleep disorders, etc.), structural modification has not clearly separated the different properties of these drugs. Testing novel benzodiazepine-like compounds, such as the sulfur analogs, may yield new drugs with a greater degree of selectivity.